Prevalence and pathology of equine parvovirus-hepatitis in racehorses from New York racetracks.

BACKGROUND: Theiler's disease, a.k.a. equine serum hepatitis, is a devastating, highly fatal disease of horses. Equine parvovirus-hepatitis (EqPV-H) has been identified as the likely cause of this disease. While the incidence of Theiler's disease is low, the prevalence of EqPV-H DNA in horses is high, with up to 37% in some regions, suggesting that subclinical or persistent infection is common. METHODS: To determine the prevalence and pathogenicity of EqPV-H infection at New York racetracks, DNA was extracted from archived formalin-fixed, paraffin-embedded liver tissues from racehorses submitted for necropsy to the Animal Health Diagnostic Center as part of the New York State Gaming Commission-Cornell University postmortem examination program. A total of 191 liver samples from horses between 2 and 13 years old were evaluated. Extracted DNA was tested for EqPV-H using PCR and gel electrophoresis. PCR-positive samples were further assessed for tissue morphology using histology and detection of viral nucleic acid using in situ hybridization. RESULTS: Forty-two samples were PCR positive (22%). Of those, 31 samples had positive viral nucleic acid hybridization in hepatocytes with 11 samples showing positive hybridization in necrotic hepatocytes associated with inflammatory cells, indicating active hepatitis. Both individual hepatocyte necrosis and hepatitis were positively associated with EqPV-H detection (p < 0.0001 and p = 0.0005, respectively). CONCLUSION: These findings indicate that presence of EqPV-H in the liver and parvoviral-associated hepatitis are prevalent in racehorses from New York racetracks, thus warranting additional studies examining potential associations between EqPV-H infection and racehorse performance.

Using the Residency Matched Method and Intent to Practice Method to Estimate Primary Care Workforce Production.

Introduction: Many medical schools overestimate the percentage of their graduates who enter the primary care workforce based on the "first-certificate" residency their graduates enter. To rectify this problem, Deutchman and colleagues proposed a new method of estimation. The objective of this study was to compare results from the traditional residency match and Deutchman methods to the actual percentage of University of Kansas School of Medicine (KUSM) graduates who practice primary care after completing medical school and all residency and subspeciality fellowship training. Methods: A retrospective study was conducted using a convenience sample of KUSM graduates from 2003-2014. Percentages of graduates classified as primary care by the traditional Residency Match Primary Care Method (RMPCM) and the percentages of graduates identified as primary care by Deutchman's Intent to Practice Primary Care Method (IPPCM) were compared with the actual percentage of graduates who eventually entered the primary care workforce. Results: Of the 1,944 KUSM graduates identified during the study period, the RMPCM predicted a 48.1% primary care output rate. The Deutchman's IPPCM predicted a 22.8% primary care output rate. The actual known percentage of graduates practicing primary care was 34.2%. Conclusions: Neither the RMPCM nor the Deutchman's IPPCM performed well in predicting the percentage or number of KUSM graduates who eventually practiced primary care. Due to predictions for the shortage of primary care physicians, there is a need to identify a method that more accurately predicts the medical schools' contribution to the primary care workforce.

Diagnosis in a snap: a pilot study using Snapchat in radiologic didactics.

PURPOSE: To evaluate Snapchat, an image-based social media platform, as a tool for emergency radiologic didactics comparing image interpretation on mobile devices with conventional analysis on a classroom screen. MATERIALS AND METHODS: Seven radiology residents (4 juniors, 3 seniors;4 males, 3 females; 28.4 years old, ± 1.7 years) were shown 5 emergent radiologic cases using Snapchat and 5 cases of similar content and duration on a classroom projector over 4 weeks. All images depicted diagnoses requiring immediate communication to ordering physicians. Performance was scored 0-2 (0 = complete miss, 1 = major finding, but missed the diagnosis, 2 = correct diagnosis) by two attending radiologists in consensus. RESULTS: All residents performed better on Snapchat each week. In weeks 1-4, juniors scored 21/40 (52.5%), 23/40 (57.5%), 19/40 (47.5%), and 18/40 (45%) points using Snapchat compared with 13/40 (32.5%), 23/40 (57.5%), 14/40 (35%), and 13/40 (32.5%), respectively, each week by projector, while seniors scored 19/30 (63.3%), 21/30 (70%), 27/30 (90%), and 21/30 (70%) on Snapchat versus 16/30 (53.3%), 19/30 (63.3%), 20/30 (66.7%), and 20/30 (66.7%) on projector. Four-week totals showed juniors scoring 81/160 (50.6%) on Snapchat and 63/160 (39.4%) by projector compared with seniors scoring 88/120 (73.3%) and 75/120 (62.5%), respectively. Performance on Snapchat was statistically, significantly better than via projector during weeks 1 and 3 (p values 0.0019 and 0.0031). CONCLUSION: Radiology residents interpreting emergency cases via Snapchat showed higher accuracy compared with using a traditional classroom screen. This pilot study suggests that Snapchat may have a role in the digital radiologic classroom's evolution.

Palliative space-time: Expanding and contracting geographies of US health care.

Two important changes are happening in health care in the US. As hospitals close in high numbers, the geographies of health care services are changing. Also, the ageing of the population brings about new and complex care needs. These are not discrete trends, as ageing impacts the who, what, and where of care needs, and hospital closures remakes the geographies of where people overall access care. Developed out of research on the impacts of hospital restructuring on workers, patients, and communities, this paper aims to understand how health care financing, care needs for the ageing, and new geographies of health services are intertwined. To do so, I look back to 1980s policy changes to Medicare, the federal health insurance program for the elderly and disabled. In 1982, Congress made two important changes to Medicare. The program began covering hospice services, constituting an expansion of care, and the government drastically changed the way it reimburses providers, effectively a contraction of the program. I trace the impacts of these changes over the next decades through analysis of media coverage and secondary research on hospital budgets. Drawing on the concept of palliative space-time, I identify a contradictory logic of death at the center of this expansion and contraction of the health care system. This death logic works to destabilize an already uneven geography of health service. Yet, this crisis has the potential for more just geographies of health and care.

Physical activity prevents acute inflammation in a gout model by downregulation of TLR2 on circulating neutrophils as well as inhibition of serum CXCL1 and is associated with decreased pain and inflammation in gout patients.

OBJECTIVES: Gout is the most prevalent inflammatory arthritis. To study the effects of regular physical activity and exercise intensity on inflammation and clinical outcome, we examined inflammatory pathogenesis in an acute model of murine gout and analyzed human gout patient clinical data as a function of physical activity. METHODS: NF-κB-luciferase reporter mice were organized into four groups and exercised at 0 m/min (non-exercise), 8 m/min (low-intensity), 11 m/min (moderate-intensity), and 15 m/min (high-intensity) for two weeks. Mice subsequently received intra-articular monosodium urate (MSU) crystal injections (0.5mg) and the inflammatory response was analyzed 15 hours later. Ankle swelling, NF-κB activity, histopathology, and tissue infiltration by macrophages and neutrophils were measured. Toll-like receptor (TLR)2 was quantified on peripheral monocytes/neutrophils by flow cytometry and both cytokines and chemokines were measured in serum or synovial aspirates. Clinical data and questionnaires accessing overall physical activity levels were collected from gout patients. RESULTS: Injection of MSU crystals produced a robust inflammatory response with increased ankle swelling, NF-κB activity, and synovial infiltration by macrophages and neutrophils. These effects were partially mitigated by low and moderate-intensity exercise. Furthermore, IL-1ß was decreased at the site of MSU crystal injection, TLR2 expression on peripheral neutrophils was downregulated, and expression of CXCL1 in serum was suppressed with low and moderate-intensity exercise. Conversely, the high-intensity exercise group closely resembled the non-exercised control group by nearly all metrics of inflammation measured in this study. Physically active gout patients had significantly less flares/yr, decreased C-reactive protein (CRP) levels, and lower pain scores relative to physically inactive patients. CONCLUSIONS: Regular, moderate physical activity can produce a quantifiable anti-inflammatory effect capable of partially mitigating the pathologic response induced by intra-articular MSU crystals by downregulating TLR2 expression on circulating neutrophils and suppressing systemic CXCL1. Low and moderate-intensity exercise produces this anti-inflammatory effect to varying degrees, while high-intensity exercise provides no significant difference in inflammation compared to non-exercising controls. Consistent with the animal model, gout patients with higher levels of physical activity have more favorable prognostic data. Collectively, these data suggest the need for further research and may be the foundation to a future paradigm-shift in conventional exercise recommendations provided by Rheumatologists to gout patients.

Pathological manifestation of autoimmune myocarditis is detected prior to glomerulonephritis in a murine model of lupus nephritis.

OBJECTIVE: Since enhanced cardiac magnetic resonance imaging (cMRI) signals have been associated with lupus disease activity in humans prior to renal failure and novel, cardiac-focused therapeutic strategies could be investigated with an associated animal model, autoimmune myocarditis was characterized in murine lupus nephritis (NZM2410). METHODS: Weekly blood urea nitrogen (BUN) levels and weights were recorded. Cardiac function was assessed by echocardiogram. Myocardial edema was measured with quantitative T2 cMRI mapping. Endpoint serum and cardiac tissue were collected for histopathological analysis and cytokine measurements. RESULTS: Despite showing no signs of significant renal disease, mice displayed evidence of myocarditis and fibrosis histologically at 30-35 weeks. Moreover, T2 cMRI mapping displayed robust signals and analysis of sagittal heart sections showed significant myocardium thickening. Cytokine expression levels of IL-2, IL-10, TNF-α, CXCL1, and IL-6 were significantly enhanced in serum. Echocardiograms demonstrated significantly increased ventricular diameters and reduced ejection fractions, while immunohistochemical staining identified CD4+ and CD8+ T cells, and IL-17 in cardiac infiltrates. Human lupus cardiac tissue showed similar histopathology with enhanced infiltrates by H&E, fibrosis, and CD4+ detection. CONCLUSIONS: Histopathology, functional abnormalities, and enhanced cMRI signals indicative of myocarditis are detected in NZM2410 mice without glomerulonephritis, which supports the primary pathological role of autoimmune-mediated, cardiac-targeted inflammation in lupus.

In vitro Crosslinking Reactions and Substrate Incorporation Assays for The Identification of Transglutaminase-2 Protein Substrates.

Transglutaminase (TG2) catalyzes protein crosslinking between glutamyl and lysyl residues. Catalytic activity occurs via a transamidation mechanism resulting in the formation of isopeptide bonds. Since TG2-mediated transamidation is of mechanistic importance for a number of biological processes, assays that enable rapid and efficient identification and characterization of candidate substrates are an important first-step to uncovering the function of crosslinked proteins. Herein we describe an optimized and flexible protocol for in vitro TG2 crosslink reactions and substrate incorporation assays. We have previously employed these techniques in the identification of the protein high mobility group box 1 (HMGB1) as a TG2 substrate. However, the protocol can be adapted for identification of any candidate transamidation substrate.

Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes-MELAS Syndrome.

BACKGROUND: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. CASE REPORT: We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. CONCLUSION: This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy.

The association of a novel haplotype in the dopamine transporter with preschool age posttraumatic stress disorder.

OBJECTIVE: Significant evidence supports a genetic contribution to the development of posttraumatic stress disorder (PTSD). Three previous studies have demonstrated an association between PTSD and the nine repeat allele of the 3' untranslated region (3'UTR) variable number tandem repeat (VNTR) in the dopamine transporter (DAT, rs28363170). Recently a novel, functionally significant C/T single-nucleotide polymorphism (SNP) in the 3'UTR (rs27072) with putative interactions with the 3'VNTR, has been identified. To provide enhanced support for the role of DAT and striatal dopamine regulation in the development of PTSD, this study examined the impact of a haplotype defined by the C allele of rs27072 and the nine repeat allele of the 3'VNTR on PTSD diagnosis in young trauma-exposed children. METHODS: DAT haplotypes were determined in 150 trauma-exposed 3-6 year-old children. PTSD was assessed with a semistructured interview. After excluding double heterozygotes, analysis was performed on 143 total subjects. Haplotype was examined in relation to categorical and continuous measures of PTSD, controlling for trauma type and race. Additional analysis within the two largest race categories was performed, as other means of controlling for ethnic stratification were not available. RESULTS: The number of haplotypes (0, 1, or 2) defined by the presence of the nine repeat allele of rs28363170 (VNTR in the 3'UTR) and the C allele of rs27072 (SNP in the 3'UTR) was significantly associated with both the diagnosis of PTSD and total PTSD symptoms. Specifically, children with one or two copies of the haplotype had significantly more PTSD symptoms and were more likely to be diagnosed with PTSD than were children without this haplotype. CONCLUSIONS: These findings extend previous findings associating genetic variation in the DAT with PTSD. The association of a haplotype in DAT with PTSD provides incremental traction for a model of genetic vulnerability to PTSD, a specific underlying mechanism implicating striatal dopamine regulation, and insight into potential future personalized interventions.